POS0182 WHO ARE LIKELY TO BENEFIT FROM THE GOOD LIFE WITH OSTEOARTHRITIS IN DENMARK (GLAD) EXERCISE AND EDUCATION PROGRAM? AN EFFECT MODIFIER ANALYSIS OF A RANDOMISED CONTROLLED TRIAL
Authors: M. Henriksen, S. M. Nielsen, R. Christensen, L. E. Kristensen, H. Bliddal, C. R. Bartholdy, M. Boesen, D. Hunter, R. Altman, E. Bandak
Journal: Annals of the Rheumatic Diseases (2022)

Background EULAR clinical guidelines have identified moderators of knee osteoarthritis (OA) outcomes as an important research priority to optimize individualized treatment. In our recent trial the GLAD exercise and education program was proved equivalent to open-label placebo (OLP) in 206 people with knee OA, which calls for evaluation of factors that may predict differential treatment response to GLAD versus OLP. Objectives To identify contextual factors that might modify the treatment effect of the ‘ Good Life with osteoArthritis in Denmark ’ (GLAD) exercise and education programme on knee osteoarthritis (OA) pain compared to that of open-label placebo (OLP) in individuals with knee OA, i.e. explore who are likely to benefit from participating in exercise and education programs. Methods Secondary effect modifier analysis of a randomised controlled trial, in which 206 adults aged ≥ 50 years, with symptomatic and radiographic knee OA were randomised to either an 8-week exercise and education programme (GLAD; n=102) or OLP in the form of 4 intra-articular saline injections over 8 weeks (n=104). Primary outcome was change from baseline to week 9 in the Knee injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale (range 0 (worst) to 100 (best)). Subgroups were created based on baseline information: BMI, swollen study knee, bilateral radiographic knee OA, sports participation as a young adult, sex, median age, a priori treatment preference, regular use of analgesics (NSAIDs or paracetamol), radiographic disease severity, and presence of constant and intermittent pain using the Intermittent and Constant Osteoarthritis Pain questionnaire. Analyses were based on the intention-to-treat principle with simple conservative non-responder imputation of missing outcome data. Results Participants who at baseline reported use of analgesics at baseline seem to benefit from the GLAD programme over OLP (subgroup contrast: 10.3 KOOS pain points (95% CI 3.0 to 17.6)). Further, participants with constant pain at baseline also seem to benefit from GLAD over OLP (subgroup contrast: 10.0 KOOS pain points (95%CI 2.8 to 17.2; P =0.007)). Further, a priori preference for GLAD also seemed to predict treatment effect in favour of GLAD. Presence of intermittent pain predicted beneficial effects of OLP, albeit the precision of the estimate was low. See Figure 1. Figure 1. Forest plot showing the results of the subgroup analyses based on the intention-to-treat population with missing outcome data at week 9 replaced with the baseline observation (non-responder imputation). The outcome is change from baseline in KOOS pain at week 9 (after 8 weeks of intervention). GLAD: The Good Life with osteoArthritis in Denmark exercise and education programme. OLP: Open-label placebo consisting of 4 intra-articular saline injections. K-L: Kellgren-Lawrence grading of radiographic disease severity. The full vertical line indicates the overall treatment effect, and the dashed line indicates zero effect. *24 GLAD and 26 OLP had no preference and are not included in the analyses, and 8 GLAD and 5 OLP had missing data; †For study knee. Conclusion These results imply that GLAD should not be considered as a one-size-fits-all intervention. For patients who take analgesics for their knee pain or report constant knee pain, GLAD seems to yield clinically relevant benefits when compared to an open-label placebo. The results support a stratified recommendation of GLAD as management of knee OA. Disclosure of Interests None declared